{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:19:13Z","timestamp":1780507153066,"version":"3.54.1"},"reference-count":50,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:p>\n                    It has been difficult to separate\/identify the roles of ClC-2 and CFTR in Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    transport studies. Using pharmacological agents, we aimed to differentiate functionally between ClC-2 and CFTR Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    channel currents. Effects of CFTR inhibitor 172 (CFTR\n                    <jats:sub>inh<\/jats:sub>\n                    172), N-(4-methylphenylsulfonyl)- N\u2032-(4-trifluoromethylphenyl)urea (DASU-02), and methadone were examined by whole cell patch clamp on Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    currents in recombinant human ClC-2\/human embryonic kidney 293 (ClC-2\/HEK293) cells stably transformed with Epstein-Barr nuclear antigen 1 (hClC-2\/293EBNA) and human CFTR\/HEK293 (hCFTR\/HEK293) cells and by short-circuit current ( I\n                    <jats:sub>sc<\/jats:sub>\n                    ) measurements in T84 cells. Lubiprostone and forskolin-IBMX were used as activators. CFTR\n                    <jats:sub>inh<\/jats:sub>\n                    172 inhibited forskolin-IBMX-stimulated recombinant human CFTR (hCFTR) and lubiprostone-stimulated recombinant human ClC-2 (hClC-2) Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    currents in a concentration-dependent manner equipotently. DASU-02 inhibited forskolin-IBMX-stimulated Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    currents in hCFTR\/HEK293 cells, but not lubiprostone-stimulated Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    currents in hClC-2\/293EBNA cells. In T84 cells with basolateral nystatin or 1-ethyl-2-benzimidazolinone (1-EBIO), lubiprostone-stimulated and forskolin-IBMX-cyclosporin A (FICA)-stimulated I\n                    <jats:sub>sc<\/jats:sub>\n                    components were observed. CFTR\n                    <jats:sub>inh<\/jats:sub>\n                    172 inhibited major portions of both components. DASU-02 had no effect on lubiprostone-stimulated I\n                    <jats:sub>sc<\/jats:sub>\n                    but partially inhibited FICA-stimulated I\n                    <jats:sub>sc<\/jats:sub>\n                    . T84 cells in which ClC-2 or CFTR was knocked down using siRNAs were constructed. T84 ClC-2 knockdown cells did not respond to lubiprostone but did respond to forskolin-IBMX in a methadone-insensitive, DASU-02-sensitive manner, indicating CFTR function. T84 CFTR knockdown cells responded separately to lubiprostone and forskolin-IBMX in a methadone-sensitive and DASU-02-insensitive manner, indicating ClC-2 function. Low lubiprostone concentrations activated ClC-2, but not CFTR, and both channels were activated by forskolin-IBMX but have different inhibitor sensitivities. Methadone, but not DASU-02, inhibited ClC-2. DASU-02, but not methadone, inhibited CFTR. In T84 cells, both ClC-2 and CFTR are present and likely play roles in Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    secretion.\n                  <\/jats:p>","DOI":"10.1152\/ajpcell.00077.2014","type":"journal-article","created":{"date-parts":[[2014,7,9]],"date-time":"2014-07-09T23:05:33Z","timestamp":1404947133000},"page":"C479-C492","source":"Crossref","is-referenced-by-count":34,"title":["Differentiation between human ClC-2 and CFTR Cl\n                    <sup>\u2212<\/sup>\n                    channels with pharmacological agents"],"prefix":"10.1152","volume":"307","author":[{"given":"John","family":"Cuppoletti","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayati","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular 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